ORIGINAL ARTICLE

A shift to a peripheral Th2-type cytokine pattern during the carcinogenesis of cervical cancer becomes manifest in CIN III lesions

A G Bais¹, I Beckmann¹, J Lindemans², P C Ewing³, C J L M Meijer⁴, P J F Snijders⁴ and T J M Helmerhorst¹

¹ Department of Obstetrics and Gynaecology, Erasmus University Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands
² Department of Clinical Chemistry, Erasmus University Medical Centre
³ Department of Pathology, Erasmus University Medical Centre
⁴ Department of Pathology, Vrije Universiteit Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands

Correspondence to:
Correspondence to:
Professor T J M Helmerhorst
Department of Obstetrics and Gynaecology, Erasmus University Medical Centre Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands; t.helmerhorst{at}erasmusmc.nl

Background: A shifted balance between T helper 1 (Th1)-type and Th2-type cytokines has been hypothesised in cervical dysplasia

Aims: To evaluate possible deregulation of the cytokine network by estimating the expression of peripheral cytokines in different stages of cervical disease and in relation to the presence or absence of high risk human papillomavirus (HR-HPV).

Methods: Twenty one HR-HPV positive women with high grade cervical intraepithelial neoplasia (CIN II–III) and 12 patients with invasive cervical carcinoma formed the study groups. Two control groups consisted of 10 HR-HPV positive and 11 HR-HPV negative women without CIN. Differences in leucocyte subgroups were evaluated by a differential leucocyte count. Plasma concentrations of tumour necrosis factor (TNF), TNF receptors TNFRI and TNFRII, interferon (IFN), interleukin 2 (IL-2), IL-12, IL-4, and IL-10 were determined by enzyme linked immunosorbent assays.

Results: Leucocyte counts in patients with CIN III and carcinoma were significantly higher than in controls. Plasma IFN concentrations were significantly lower in patients with CIN III and carcinoma than in women with CIN II or controls. Plasma concentrations of IL-12, IL-2, IL-4, and TNF did not differ significantly between groups, but significantly lower plasma concentrations of TNFRII were found in CIN III and carcinoma compared with CIN II. IL-10 was detected with increased frequency in the plasma of patients with CIN III and carcinoma.

Conclusions: These results indicate that a shift to a Th2-type cytokine pattern during the carcinogenesis of cervical cancer occurs in women with CIN III lesions.

Abbreviations: CIN, cervical intraepithelial neoplasia; CV, coefficient of variation; HPV, human papillomavirus; HR, high risk; IFN, interferon ; IL, interleukin; MDC, minimal detectable concentration; PCR, polymerase chain reaction; s, soluble; Th, T helper; TNF, tumour necrosis factor ; TNFR, tumour necrosis factor receptor

Keywords: cervical dysplasia; peripheral cytokines; high risk human papillomavirus

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